tbuckley/cabot-search huggingface dataset:
Cardiovascular Risk and Use of Estrogens or Estrogen-Progestagen Combinations
Authors: Michael P. Stern
Journal: JAMA (1976)

Cardiovascular risk factors were assessed in 986 women residing in three northern California communities. Women who reported current use of oral contraceptives had higher plasma triglyceride levels and systolic and diastolic blood pressures compared with women not using these agents, after adjusting for age and for the greater relative leanness of oral contraceptive users. Similar increases, albeit of lesser magnitude, were observed in women who used pure estrogens. Mexican-American women appeared to be more susceptible to the effects of estrogens, perhaps as a consequence of their greater degree of obesity. (<i>JAMA</i>235:811-815, 1976)
Clinical advances: pregnancy in gastroenterologic and hepatic conditions
Authors: Sunanda V Kane, Nancy Reau
Journal: Gut (2023)

The fields of gastroenterology and hepatology, along with endoscopic practice, have seen significant changes and innovations to practice in just the past few years. These practice changes are not limited to gastroenterology, but maternal fetal medicine and the care of the pregnant person have become increasingly more sophisticated as well. Gastroenterologists are frequently called on to provide consultative input and/or perform endoscopy during pregnancy. To be able to provide the best possible care to these patients, gastroenterologists need to be aware of (and familiar with) the various nuances and caveats related to the care of pregnant patients who either have underlying gastrointestinal (GI) conditions or present with GI and liver disorders. Here, we offer a clinical update with references more recent than 2018, along with a few words about SARS-CoV-2 infection and its relevance to pregnancy.
IL-17A-producing CD8<sup>+</sup>T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts
Authors: Felix Simon Ruben Picard, Veronika Lutz, Anna Brichkina, Felix Neuhaus, Teresa Ruckenbrod, Anna Hupfer, Hartmann Raifer, Matthias Klein, Tobias Bopp, Petra Ina Pfefferle, Rajkumar Savai, Immo Prinz, Ari Waisman, Sonja Moos, Hyun-Dong Chang, Stefan Heinrich, Detlef K Bartsch, Malte Buchholz, Shiv Singh, Mengyu Tu, Lukas Klein, Christian Bauer, Robert Liefke, Andreas Burchert, Ho-Ryun Chung, Philipp Mayer, Thomas M Gress, Matthias Lauth, Matthias Gaida, Magdalena Huber
Journal: Gut (2023)

Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8
Comprehensive assessment and classification of upper and lower limb pain in athletes: a scoping review
Authors: Ciarán Purcell, Ciara Duignan, Brona M Fullen, Shiofra Ryan, Tomas Ward, Brian Caulfield
Journal: British Journal of Sports Medicine (2023)

Background Upper and lower limb (peripheral) pain is prevalent in athletes. Contemporary research prioritises multidimensional pain assessment and classification. This study aims to review comprehensive athlete pain assessment practices against the reference standard (International Olympic Committee, IOC Athlete Pain framework), identifying trends and highlighting gaps. Methods and analysis Six databases were searched using a comprehensive search strategy. This review followed the Joanna Briggs Institute standardised methodology for scoping reviews and is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Title and abstract, full-text screening and data charting were completed by two independent reviewers. Inclusion criteria Original research, systematic reviews and clinical practice guidelines reporting assessment or classification of pain in athletes of any age with chronic or acute peripheral pain in English on human participants from database inception. Results 470 studies with 175 different pain assessment tools were mapped against the IOC Athlete Pain Framework. Papers included tools from neurophysiological (470/100%), biomechanical (425/90%), affective (103/22%), cognitive (59/13%) and socioenvironmental (182/39%) domains. Pain classification was included in 108 studies (23%). 4 studies (0.85%) defined pain. Athletes with physical disability were included in 13 (3%) studies and no studies included athletes with intellectual disabilities. Socioeconomic factors were addressed in 29 (6%) studies. Discussion Neurophysiological and biomechanical domains are frequently addressed. Affective, socioenvironmental and cognitive tools are under-represented. Potential tools for use by researchers and clinicians are highlighted. Defining and classifying pain and determining predominant pain mechanisms is needed in both research and clinical practice. More work on underrepresented populations is needed. Conclusion This review informs researchers and clinicians working with athletes in pain how pain assessment and classification is currently conducted and highlights future priorities.
Radiological Manifestations of Ulcerogenic Tumors of the Pancreas
Authors: A. John Christoforidis
Journal: JAMA (1966)

This analysis of the radiological manifestations of the Zollinger-Ellison syndrome is based primarily on thorough roentgenologic studies of 14 patients treated at the Ohio State University Hospitals where this disease syndrome was first described in 1955. The early diagnosis of this syndrome and its differentiation from benign peptic ulcer disease is of great importance in planning the curative surgical treatment. The radiological examination can provide some of the most important clues for an early diagnosis. Current knowledge of the pathological physiology of this condition has been correlated with the morphologic x-ray findings.
Antibodies and Immunoglobulins
Authors: John L. Fahey
Journal: JAMA (1965)

Antibody activity is characteristic of the family of structurally related molecules known as the immunoglobulins. These proteins are also known as γ-globulins because of their relative electrophoretic mobility. Many antibodies, however, migrate more rapidly than the electrophoretic γ-globulins (Fig 1). Also, molecules unrelated to antibodies may migrate with the electrophoretic mobility of γ-globulins. For these reasons, the term "immunoglobulin" and the symbol "Ig" or "γ" have been suggested to designate the family of molecules with antibody activity.<sup>1</sup> The immunoglobulins include the normal serum components known as IgG (γG, 7S γ2-globulins), IgA (γA, γ1A or β2A-globulins), IgM (γM, 18S γ1-macroglobulins), and IgD (γD) (Fig 1). The immunoglobulins also include myeloma proteins, Bence-Jones protein, and normal urinary components which have no antibody activity but which are structurally related to the antibodies. Investigation of antibodies and of immunoglobulins has advanced rapidly in recent years with (1) separation of major structural subunits of
Alopecia in Crash Dieters
Authors: Detlef K. Goette
Journal: JAMA (1976)

Nine patients experienced profuse hair loss two to five months after starting a vigorous weight reduction program resulting in weight loss of 11.7 to 24.75 kg. Telogen counts of 25% to 50% were observed. Regrowth of hair occurred within several months. Three patients had experienced hair loss closely following a successful weight reduction program on several occasions. Rigorous caloric restriction with subsequent inadequate energy supply of the hair matrix is thought to be the cause for the precipitation of the telogen effluvium of the crash dieter. (<i>JAMA</i>235:2622-2623, 1976)
BQ.1.1, XBB.1, and XBB.1.5 neutralization after bivalent mRNA COVID-19 booster in patients with cancer
Authors: Sidse Ehmsen, Rune M. Pedersen, Line L. Bang, Anders Asmussen, Amalie Kragh, Dorte K. Holm, Thomas V. Sydenham, Thøger G. Jensen, Stefan S. Jeppesen, Henrik Frederiksen, Thomas E. Andersen, Henrik J. Ditzel
Journal: Cancer Cell (2023)
Patterns in utilization of health care services and medications among patients with cutaneous immune-related adverse events: A population-level cohort study
Authors: Bonnie W. Leung, Michael Ryan Collier, Bruce C. Tiu, Guihong Wan, Nga Nguyen, Kimberly Tang, Shijia Zhang, Wenxin Chen, Steven T. Chen, Nicole R. LeBoeuf, Yevgeniy R. Semenov
Journal: Journal of the American Academy of Dermatology (2023)
Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects
Authors: Michael J. Workman, Ryan G. Lim, Jie Wu, Aaron Frank, Loren Ornelas, Lindsay Panther, Erick Galvez, Daniel Perez, Imara Meepe, Susan Lei, Viviana Valencia, Emilda Gomez, Chunyan Liu, Ruby Moran, Louis Pinedo, Stanislav Tsitkov, Ritchie Ho, Julia A. Kaye, Terri Thompson, Jeffrey D. Rothstein, Steven Finkbeiner, Ernest Fraenkel, Dhruv Sareen, Leslie M. Thompson, Clive N. Svendsen
Journal: Neuron (2023)

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol. This is the largest set of iPSCs to be differentiated into motor neurons, and characterization suggests that cell composition and sex are significant sources of variability that need to be carefully controlled for in future studies. These data are reported as a resource for the scientific community that will utilize Answer ALS data for disease modeling using a wider array of omics being made available for these samples.
IL15 modification enables CAR T cells to act as a dual targeting agent against tumor cells and myeloid-derived suppressor cells in GBM
Authors: Markella Zannikou, Joseph T Duffy, Rebecca N Levine, Maggie Seblani, Qianli Liu, Aaron Presser, Victor A Arrieta, Christopher J Chen, Adam M Sonabend, Craig M Horbinski, Catalina Lee-Chang, Jason Miska, Maciej S Lesniak, Stephen Gottschalk, Irina V Balyasnikova
Journal: Journal for ImmunoTherapy of Cancer (2023)

Introduction The immunosuppressive tumor microenvironment (TME) is a major barrier to the efficacy of chimeric antigen receptor T cells (CAR-T cells) in glioblastoma (GBM). Transgenic expression of IL15 is one attractive strategy to modulate the TME. However, at present, it is unclear if IL15 could be used to directly target myeloid-derived suppressor cells (MDSCs), a major cellular component of the GBM TME. Here, we explored if MDSC express IL15Rα and the feasibility of exploiting its expression as an immunotherapeutic target. Methods RNA-seq, RT-qPCR, and flow cytometry were used to determine IL15Rα expression in paired peripheral and tumor-infiltrating immune cells of GBM patients and two syngeneic murine GBM models. We generated murine T cells expressing IL13Rα2-CARs and secretory IL15 (CAR.IL15s) or IL13Rα2-CARs in which IL15 was fused to the CAR to serve as an IL15Rα-targeting moiety (CAR.IL15f), and characterized their effector function in vitro and in syngeneic IL13Rα2+glioma models. Results IL15Rα was preferentially expressed in myeloid, B, and dendritic cells in patients’ and syngeneic GBMs. In vitro, CAR.IL15s and CAR.IL15f T cells depleted MDSC and decreased their secretion of immunosuppressive molecules with CAR.IL15f T cells being more efficacious. Similarly, CAR.IL15f T cells significantly improved the survival of mice in two GBM models. TME analysis showed that treatment with CAR.IL15f T cells resulted in higher frequencies of CD8+T cells, NK, and B cells, but a decrease in CD11b+cells in tumors compared with therapy with CAR T cells. Conclusions We demonstrate that MDSC of the glioma TME express IL15Ra and that these cells can be targeted with secretory IL15 or an IL15Rα-targeting moiety incorporated into the CAR. Thus, IL15-modified CAR T cells act as a dual targeting agent against tumor cells and MDSC in GBM, warranting their future evaluation in early-phase clinical studies.
Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects
Authors: Haiyan Bai, Alvaro S Padron, Yilun Deng, Yiji J Liao, Clare J Murray, Carlos Ontiveros, Suresh J Kari, Aravind Kancharla, Anand V R Kornepati, Myrna Garcia, Ryan Michael Reyes, Harshita B Gupta, Jose R Conejo-Garcia, Tyler Curiel
Journal: Journal for ImmunoTherapy of Cancer (2023)

Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies.
Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
Authors: Xiuju Wu, Daoqin Zhang, Xiaojing Qiao, Li Zhang, Xinjiang Cai, Jaden Ji, Jocelyn A. Ma, Yan Zhao, John A. Belperio, Kristina I. Boström, Yucheng Yao
Journal: European Respiratory Journal (2023)

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.
Minimal clinically important difference for impulse oscillometry in adults with asthma
Authors: Mustafa Abdo, Anne-Marie Kirsten, Erika von Mutius, Matthias Kopp, Gesine Hansen, Klaus F. Rabe, Henrik Watz, Frederik Trinkmann, Thomas Bahmer
Journal: European Respiratory Journal (2023)

Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma.We performed IOS at baseline and 1 year later in adult patients with mild-to-severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs): Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire-7 (ACQ-7) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs compared with the established MCID of forced expiratory volume in 1 s (FEV1).The proposed MCID was a decline of ≥0.06 kPa·L-1·s-1 and ≥0.65 kPa·L-1 for FDR and AX, respectively. Patients who had changes beyond the MCIDs for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCIDs for ACQ-7 and AQLQ, and approximated the MCID for ACT. Multivariable analyses demonstrated the MCIDs for both FDR and AX as independent predictors for the MCIDs of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV1.This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasises that small airway function is a distinguished end-point beyond the conventional measure of FEV1.
Leveraging explainable AI for gut microbiome-based colorectal cancer classification
Authors: Ryza Rynazal, Kota Fujisawa, Hirotsugu Shiroma, Felix Salim, Sayaka Mizutani, Satoshi Shiba, Shinichi Yachida, Takuji Yamada
Journal: Genome biology (2023)

Abstract Studies have shown a link between colorectal cancer (CRC) and gut microbiome compositions. In these studies, machine learning is used to infer CRC biomarkers using global explanation methods. While these methods allow the identification of bacteria generally correlated with CRC, they fail to recognize species that are only influential for some individuals. In this study, we investigate the potential of Shapley Additive Explanations (SHAP) for a more personalized CRC biomarker identification. Analyses of five independent datasets show that this method can even separate CRC subjects into subgroups with distinct CRC probabilities and bacterial biomarkers.
REPAC: analysis of alternative polyadenylation from RNA-sequencing data
Authors: Eddie L. Imada, Christopher Wilks, Ben Langmead, Luigi Marchionni
Journal: Genome biology (2023)

Abstract Alternative polyadenylation (APA) is an important post-transcriptional mechanism that has major implications in biological processes and diseases. Although specialized sequencing methods for polyadenylation exist, availability of these data are limited compared to RNA-sequencing data. We developed REPAC, a framework for the analysis of APA from RNA-sequencing data. Using REPAC, we investigate the landscape of APA caused by activation of B cells. We also show that REPAC is faster than alternative methods by at least 7-fold and that it scales well to hundreds of samples. Overall, the REPAC method offers an accurate, easy, and convenient solution for the exploration of APA.
Pervasiveness of HLA allele-specific expression loss across tumor types
Authors: Ioan Filip, Anqi Wang, Oleksandr Kravets, Rose Orenbuch, Junfei Zhao, Tomin E. Perea-Chamblee, Gulam A. Manji, Evangelina López de Maturana, Núria Malats, Kenneth P. Olive, Raul Rabadan
Journal: Genome Medicine (2023)

Efficient presentation of mutant peptide fragments by the human leukocyte antigen class I (HLA-I) genes is necessary for immune-mediated killing of cancer cells. According to recent reports, patient HLA-I genotypes can impact the efficacy of cancer immunotherapy, and the somatic loss of HLA-I heterozygosity has been established as a factor in immune evasion. While global deregulated expression of HLA-I has also been reported in different tumor types, the role of HLA-I allele-specific expression loss - that is, the preferential RNA expression loss of specific HLA-I alleles - has not been fully characterized in cancer.Here, we use RNA and whole-exome sequencing data to quantify HLA-I allele-specific expression (ASE) in cancer using our novel method arcasHLA-quant.We show that HLA-I ASE loss in at least one of the three HLA-I genes is a pervasive phenomenon across TCGA tumor types. In pancreatic adenocarcinoma, tumor-specific HLA-I ASE loss is associated with decreased overall survival specifically in the basal-like subtype, a finding that we validated in an independent cohort through laser-capture microdissection. Additionally, we show that HLA-I ASE loss is associated with poor immunotherapy outcomes in metastatic melanoma through retrospective analyses.Together, our results highlight the prevalence of HLA-I ASE loss and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment.
Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases
Authors: Chong Zhang, Xiang-Yu Wang, Jie-Liang Zuo, Xue-Fu Wang, Xiao-Wen Feng, Bo Zhang, Yi-Tong Li, Chen-He Yi, Peng Zhang, Xiao-Chen Ma, Zhen-Mei Chen, Yue Ma, Jia-Hao Han, Bao-Rui Tao, Rui Zhang, Tian-Qi Wang, Li Tong, Wang Gu, Si-Yu Wang, Xiao-Fei Zheng, Wen-Kang Yuan, Zi-Jie Kan, Jie Fan, Xiang-Yang Hu, Jun Li, Chao Zhang, Jin-Hong Chen
Journal: Journal for ImmunoTherapy of Cancer (2023)

Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.
On Trends in the Diagnosis of Schizophrenia
Authors: Judith B. Kuriansky, W. Edwards Deming, Barry J. Gurland
Journal: American Journal of Psychiatry (1974)

A reexamination of hospital diagnoses made at New York State Psychiatric Institute in 1932–1941 and 1947–1956 (64 in each decade) indicated that the original diagnosticians used a broader concept of schizophrenia in the second decade (77 percent of the 64 cases) than in the first (28 percent). Rediagnoses by 16 American-trained psychiatrists showed practically no change between the decades (42 and 47 percent), while a British-trained psychiatrist rediagnosed more cases of schizophrenia in the first decade (31 percent) than in the second (19 percent). The authors believe these differences may be due to a decrease in the number of "hard-core" schizophrenics while the number of "ambiguous" schizophrenics increased, inviting more diagnoses of schizophrenia by those with a broader concept of schizophrenia.